Immunological resistance to infectious disease depends on hereditary factors. Genes control lymphoid cell maturation and intercellular cooperative networks producing a response appropriate to the foreign stimulus. Defined immune response (Ir) genes in mice provide an opportunity to study mechanisms governing immunity. A prerequisite to explaining Ir gene function(s) is to identify Ir gene products. We described a set of I-region gene controlled structures, Iat antigens, on mature T lymphocytes. We hypothesize that T cell-derived molecules or T lymphocytes expressing Iat determinants participate in immunoregulatory communication among interacting lymphocytes during an immune response. We will continue our Iat antigen studies. We will characterize new Iat determinants and produce monoclonal Iat-specific antibodies. We will use these antibodies to isolate Iat antigens and to study their chemistry, synthesis, turnover, enzymatic lability, expression on resting and activated T cells and allelic exclusion on T-cell subsets. Seeking to correlate Iat antigen expression and T-cell function, we studied cell-mediated immunity to weakly immunogenic minor histocompatibility antigens. Iat antiserum treatment of responding cells enhances subsequent cytotoxic T-cell development. Our experiments suggest that Iat antiserum may stimulate a helper cell. The product of this stimulation may be a soluble mediator capable of amplifying cell-mediated immunity. We will characterize the affected cell(s), identify some properties of the mediator and assess whether antigen is required for mediator production. We will probe the temporal relationship between Iat antiserum administration and antigen stimulation and compare antigen-primed with unprimed cells. Finally, we will extend our experiments to weakly immunogenic tumor-specific antigens.